[Molecular Classification of Medulloblastoma]

Medulloblastoma is the most common malignant brain tumor in children. Advances in sequencing technologies have allowed the identification of four major molecular subgroups, each defined by distinct genetic alterations, biological features, and clinical courses. Recent studies have shown that medulloblastomas arise following disruptions in normal neurodevelopment, in which genetic abnormalities impair differentiation and lead to the persistence and malignant transformation of normally eliminated progenitor cells. Subgroup-specific cell of origin have since been identified. In Group 3 and Group 4, which were previously poorly understood, genetic alterations were shown to impair neuronal differentiation, revealing their pathogenesis. In SHH medulloblastomas, mutations in genes associated with RNA biology, including ELP1 and U1 snRNA, highlight alternative mechanisms of tumor development. Each subgroup can be further divided into subtypes that enable finer distinctions between clinical outcomes, support treatment intensification in high-risk patients, and de-escalation strategies in favorable groups. Although medulloblastoma is one of the best-studied pediatric brain tumors, its complexity continues to present challenges, and a deeper understanding of its molecular heterogeneity is essential to advance risk-adapted and targeted therapies.